Cryptosporidium parvum causes life-threatening diarrheal disease in persons with AIDS. The mechanisms by which the immune system limits infection in immunocompetent hosts have not been defined. However, antibodies directed against cryptosporidial antigens have been shown to neutralize the infective stages (sporozoites and merozoites); to reduce the intensity of infection when given prophylactically in animals; and to improve or resolve disease in immuno-compromised patients when given in established infection. We have utilized the SIV/macaque model system to investigate the immune responses to cryptosporidial antigens in immune competent and immunocompromised hosts. SIV-infected rhesus macaques, in various stages of SIV- related disease (e.g. various levels of CD4+ T lymphocyte counts) were inoculated orally with varying doses (100-1000) of infectious Cryptosporidium oocysts, and monitored for clinical disease and oocyst shedding in feces. Serum, saliva, and rectal lavage samples were collected and stored at regular intervals post-inoculation with oocysts, for evaluation of secretory and peripheral antibody response to cryptosporidial antigens. Post-mortem, samples of the intra-eptihelial lymphocyte (IEL) and lamina propria lymphocyte (LPL) populations were harvested from different regions of the gut (duodenum, ileum, jejunum, and colon). These cell populations were phenotypically characterized by FACS, and were cultured and stimulated with several recombinant expressed cryptosporidial antigens. Preliminary data suggest that these lymphocyte subpopulations are quite distinct, both in terms of phenotype, and in stimulatory responses to specific cryptosporidial antigens. These on-going studies will elucidate the immune mechanisms involved in response to cryptosporidiosis in immune competent and immunocompromised hosts, specifically the relative contributions of cell-mediated immunity and secretory antibody response, and provide a model system to study the pathogenesis of chronic cryptosporidiosis in AIDS. *KEY*Cryptosporidium, AIDS, SIV, Macaques, Immune response.